This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ?-crystallin is the major structural protein of the mammalian lens and consists of two subunits, ?-A and ?-B. In addition to its role as a structural protein, a-crystallin contributes to the refractive properties of the lens and has been shown to exhibit chaperone activity. In solution, it exists in aggregate form with a distribution of molecular weights. This broad distribution of aggregate size is thought to be responsible for the unsuccessful attempts at crystallizing the protein. Computational modeling of ?-crystallin aggregates and studies on the interactions between subunits are essential for determining the tertiary and quaternary structures of ?-crystallin and may give guidance toward successful crystallization. Our current models for the subunits are built up by the fold recognition method and then refined by molecular mechanics programs. Models for ?-crystallin dimers are built up by the docking method according to the surface complementary principle and molecular dynamic programs NAMD and VMD are used to simulate the dimers at equilibrium. In addition, the Ligplot program is used to study the interactions between the subunits. Preliminary molecular dynamic studies and steered dynamic simulations calculations have been carried out for one nanosecond on the dimmer. These calculations indicate that hydrogen bonds and hydrophobic interactions play very important roles in subunit binding;the preliminary model indicates Trp60 in ?-B is included in the interactions between the subunits and this is in agreement with previous experimental results[1]. In order to extend this work and obtain further details on subunit interactions, molecular dynamic studies on both larger ?-crystallin aggregates and with longer simulation time, e.g. one microsecond, are needed. We believe that the NCSA Teragrid cluster is an invaluable resource for these studies. Reference: 1. McDermott, M., Chiesa, R., Roberts, J.E., Dillon, J. (1991) Biochemistry 30, 8653-8660